Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In primary hyperparathyroidism, bone remodeling is increased due to an enhanced activation frequency which is caused by excessive PTH. In mild cases, eroded, osteoid and labeled surfaces are increased. But as bone balance per remodeling cycle in cancellous bone is zero or even slightly positive, bone volume and structure are relatively maintained. In advanced cases, bone resorption is predominant in the endosteal surface of cortical bone, resulting in progressive thinning and increased porosity, cancellisation. As far cancellous bone resorption depth is deepened to occur trabecular perforation associated with fibrous tissue replacement, osteitis fibrosa.
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PMID:[Bone histomorphometric analysis in primary hyperparathyroidism]. 775 77

The mechanisms behind the influence of PHPT on the skeleton are closely connected with bone turnover. Throughout life, the skeleton is continuously renewed by bone remodeling, a process which serves the purpose of repairing damaged bone and adapting the skeleton to changes in physical load. In this process, old bone is removed by osteoclastic resorption and new bone is laid down by osteoblastic formation. Bone mass increases with growth in the first decades of life, and around the age of 30 years the peak bone mass is reached. Thereafter, as a result of mechanisms involving bone remodeling, a net bone loss is seen: 1) A reversible bone loss because of increase in the remodeling space, i.e., the amount of bone resorped but not yet reformed during the remodeling cycle. This mechanism leads to decrease in average trabecular thickness and cortical width, and to increase in cortical porosity. 2) An irreversible bone loss caused by negative bone balance, where the amount of bone formed by the osteoblasts is exceeded by the amount of bone resorbed by the osteoclasts at the same remodeling site. Consequently, progressive thinning of trabecular elements, reduced cortical width and increased cortical porosity is seen. 3) Finally, perforation of trabecular plates by deep resorption lacunae leads to complete irreversible removal of structural bone components. Parathyroid hormone, together with vitamin D, are the principal modulators in calcium homeostasis. The main actions of PTH are executed in bone and kidneys. In the kidneys, PTH increases the tubular re-absorption of calcium, thereby tending to increase serum calcium. PTH also induces increased conversion of 25(OH)-D to 1,25(OH)2-D. This last action, enhances intestinal calcium absorption and increased skeletal calcium mobilization, which further adds to the circulating calcium pool. In bone, the "acute" regulatory actions of PTH on serum calcium are probably accompliced via activation of osteocytes and lining cells. A second mechanism of PTH in bone is the regulation of bone remodeling. The action seems to be an increased recruitment from osteoblastic precursor cells and activation of mature osteoclasts. It is supposed that these responses are predominantly mediated indirectly through actions on osteoblast-like or nonosteoblast-like stromal cells, as osteoclasts themselves to not have PTH receptors. Bone metabolism and bone mass are studied by biochemical bone markers, bone histomorphometry, and densitometry. As bone markers and bone histomorphometry give information on bone metabolism from different points of view, these methods are preferably combined. Histomorphometry gives detailed information about bone turnover on cellular level, the whole remodeling sequence is described, and the bone balance can be calculated. However, they focus on a small volume, and may, therefore, not be representative for the whole skeleton. On the other hand, studies of bone markers supply general information about turnover in the whole skeleton, but they do not give facts on the bone turnover on the cellular or tissue level and bone balance. Bone densitometry is the principal method in studying bone mass, but valuable information concerning bone structure also comes from histomorphometry. Bone remodeling is considerably increased in PHPT. Studies of bone markers show increase in both resorptive and formative markers, and the increases seem to be of equivalent size. This is in agreement with histomorphometric findings and shows that the coupling between resorption and formation is preserved. By histomorphometry on iliac crest biopsies, trabecular bone remodeling is found increased by 50%, judged by the increase in activation frequency; a measure of how often new remodeling is initiated on the trabecular bone surface. In PHPT, such remodeling activity is repeated about once every year. Reconstruction of the whole remodeling sequence does not show major deviations in lengths of the resorptive and formative periods compared to normal. Furthermore, the amount of bone removed by the osteoclasts during the resorptive phase is matched by the amount of new bone formed by the osteoblasts leading to a bone balance very close to zero. Compared with trabecular bone, the turnover rate in cortical bone is considerably lower, around 10%. Remodeling of the cortical bone takes place at the endocortical, the pericortical, and the Haversian surfaces. Endocortical bone remodeling activities are very similar to trabecular remodeling activities with good correlation between individual parameters. Periosteal remodeling activity is negligible in PHPT, as it is in the normal state. Cortical porosity, which reflects the remodeling activity on the Haversian surface, is increased by 30-65% in PHPT. (ABSTRACT TRUNCATED)
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PMID:The skeleton in primary hyperparathyroidism: a review focusing on bone remodeling, structure, mass, and fracture. 1141 22

The maternal skeleton rapidly demineralizes during lactation to provide calcium to milk, responding to the stimuli of estrogen deficiency and mammary-secreted PTH-related protein. We used calcitonin/calcitonin gene-related peptide-alpha (Ctcgrp) null mice to determine whether calcitonin also modulates lactational mineral metabolism. During 21 d of lactation, spine bone mineral content dropped 53.6% in Ctcgrp nulls vs. 23.6% in wild-type (WT) siblings (P < 0.0002). After weaning, bone mineral content returned fully to baseline in 18.1 d in Ctcgrp null vs. 13.1 d in WT (P < 0.01) mice. Daily treatment with salmon calcitonin from the onset of lactation normalized the losses in Ctcgrp null mice, whereas calcitonin gene-related peptide-alpha or vehicle was without effect. Compared with WT, Ctcgrp null mice had increased circulating levels of PTH and up-regulation of mammary gland PTH-related protein mRNA. In addition, lactation caused the Ctcgrp null skeleton to undergo more trabecular thinning and increased trabecular separation compared with WT. Our studies confirm that an important physiological role of calcitonin is to protect the maternal skeleton against excessive resorption and attendant fragility during lactation and reveal that the postweaning skeleton has the remarkable ability to rapidly recover even from losses of over 50% of skeletal mineral content.
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PMID:Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation. 1691 34

Considering the aging dialysis population of today, increasing our knowledge about the nature, diagnosis and the treatment of bone mineral density (BMD) problems in end-stage renal disease (ESRD) patients deserves more attention. Osteoporosis is basicly defined as a decrease in bone mass. Large epidemiological studies in general population have identified several risk factors for osteoporosis including advancing age, female gender, white race, decreased calcium intake, gastric acid suppression therapy, sedentary lifestyle, premature loss of gonadal function, decreased estrogen secretion, thin body habitus, decreased physical activity, cigarette smoking, alcohol abuse, excess glucocorticoid exposure, and possibly some genetic factors. Osteoporosis in ESRD patients is only a part of a wider spectrum of metabolic bone problems, namely uremic osteodystrophy. Therefore, its diagnosis, management and follow-up may differ from the general population and an individualization of diagnosis and definition for dialysis population may be necessary. However, standard diagnostic tools such as dual energy X-ray absorptiometry (DEXA) have been widely used for the assessment of bone mineral deficiency status in ESRD patients. Regardless of the methods, most of the studies are in concordance with a reduced BMD in HD and PD patients. Dialysis patients are known to be at increased risk for low-trauma fractures. Thinning of cortical bone, which is responsible for the largest contribution toward reduced bone mineral content in chronic renal failure results in increased fracture risk. In either normal population and dialysis patients, fracture risk is increased with age. But in dialysis patients, besides age, several other factors may also affect the degree of bone mineral deficiency, and age-BMD relationship may be blunted. Female sex, in hemodialysis patients is negatively associated with total hip BMD. While several studies have been unable to demonstrate any association between BMD and PTH levels, larger body size has been shown to have a significant positive effect on BMD in both hemodialysis and peritoneal dialysis patients. Although they have been used in small groups of chronic kidney disease (CKD) and ESRD patients, because of their potential nephrotoxicity and hypocalcemic effects, use of biphosphonates in renal patients is questionable. Currently, bone biopsy, in order to exclude adynamic bone disease is recommended before beginning treatment with bisphosphonates in chronic kidney disease and dialysis patients.
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PMID:Osteoporosis in the elderly with chronic kidney disease. 1710 30

A significant portion of milk calcium comes from the mother's skeleton, and lactation is characterized by rapid bone loss. The most remarkable aspect of this bone loss is its complete reversibility, and the time after weaning is the most rapid period of skeletal anabolism in adults. Despite this, little is known of the mechanisms by which the skeleton repairs itself after lactation. We examined changes in bone and calcium metabolism defining the transition from bone loss to bone recovery at weaning in mice. Bone mass decreases during lactation and recovers rapidly after weaning. Lactation causes changes in bone microarchitecture, including thinning and perforation of trabecular plates that are quickly repaired after weaning. Weaning causes a rapid decline in urinary C-telopeptide levels and stimulates an increase in circulating levels of osteocalcin. Bone histomorphometry documented a significant reduction in the numbers of osteoclasts on d 3 after weaning caused by a coordinated wave of osteoclast apoptosis beginning 48 h after pup removal. In contrast, osteoblast numbers and bone formation rates, which are elevated during lactation, remain so 3 d after weaning. The cessation of lactation stimulates an increase in circulating calcium levels and a reciprocal decrease in PTH levels. Finally, weaning is associated with a decrease in levels of receptor activator of nuclear factor-kappaB ligand mRNA in bone. In conclusion, during lactation, bone turnover is elevated, and bone loss is rapid. Weaning causes selective apoptosis of osteoclasts halting bone resorption. The sudden shift in bone turnover favoring bone formation subsequently contributes to the rapid recovery of bone mass.
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PMID:Weaning triggers a decrease in receptor activator of nuclear factor-kappaB ligand expression, widespread osteoclast apoptosis, and rapid recovery of bone mass after lactation in mice. 1749 7

Although the role of PTH (parathyroid hormone) has been debated in glucocorticoid (GC)-induced osteoporosis (GIO), clinical data about the relation of endogenous PTH to bone metabolism in patients treated with GC are still lacking. The present study was performed to examine the relationship of PTH to bone metabolic indices, bone mineral density (BMD), and bone geometry in 174 female patients treated with oral GC for more than 6 months. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were employed for the assessment of BMD and bone geometry. No elevation of serum PTH levels was observed in patients treated with GC. Although serum levels of osteocalcin were not related to serum PTH levels, urinary levels of deoxypiridinoline were positively correlated. Serum PTH levels were negatively related to BMD at any site. In pQCT, serum PTH levels were negatively correlated to both trabecular and cortical volumetric BMD. As for bone morphometric indices, serum PTH levels were significantly related to endocortical circumferences, cortical thickness, and cortical area. Moreover, serum PTH levels were significantly higher in patients with vertebral fractures, compared with those without vertebral fractures in GC-treated patients. In the present study, serum PTH levels were related to the elevation of bone resorption marker, decreased BMD, cortical thinning, and an increase of vertebral fracture risk. The elevation of sensitivity to PTH in bone might play some role in the pathogenesis of GIO.
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PMID:Relationship between endogenous parathyroid hormone and bone metabolism/geometry in female patients treated with glucocorticoid. 1807 75

Several studies suggest that mild PTH excess does not have any deteriorative effects on bone mineral density (BMD) in several-year-longitudinal studies of patients with mild primary hyperparathyroidism (pHPT) without parathyroidectomy (PTX). However, it remains unknown about the change in bone geometry in pHPT patients without PTX. We examined the longitudinal effects of mild PTH excess on cortical bone geometry in postmenopausal patients with mild pHPT without PTX by using peripheral quantitative computed tomography (pQCT), and we compared them with normal and hypoparathyroidism women. Nine postmenopausal female patients who were diagnosed as pHPT, six postmenopausal female patients with hypoparathyroidism (3 idiopathic and 3 postoperative), and thirty postmenopausal control subjects participated in this study. Radial volumetric (v) BMD and several bone geometry parameters were measured by pQCT at basal line and after 2 years. Cortical vBMD was significantly lower in pHPT group. Moreover, total area and periosteal circumferences were significantly higher in pHPT group. Total and cortical vBMD were significantly decreased after 2 years in control group. However, they were stable in pHPT group after 2-year follow-up. As for bone geometry, cortical thickness and area were also stable in pHPT group during 2-year follow-up, although they were significantly reduced in control group and hypoparathyroidism group. In conclusion, the present longitudinal study revealed that there were no significant changes in radial vBMD and cortical bone geometry in postmenopausal women with mild pHPT, whereas age-related thinning of cortical bone as well as decrease of vBMD were observed in the control and patients with hypoparathyroidism.
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PMID:Two-year longitudinal changes in forearm cortical bone geometry in postmenopausal women with mild primary hyperparathyroidism without parathyroidectomy. 1905 30